The long-term goal is to determine the toxic impact of environmental agents on the olfactory mucosa and neighboring head and neck organs. The specific aims for this proposal are: (1). To identify and characterize P450 gene expression in adult and fetal human nasal mucosa. The cellular distribution and developmental expression of various P450 isoforms known to be active in the metabolism of foreign compounds will be examined, including CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 2F1, 3A4, 3A5, 3A7, and 4B1. These studies will broaden our knowledge of the molecular basis for risk assessment of potential toxicants in humans and may have implications in the vulnerability of the nasal tissue in the perinatal period. (2). To determine whether patients with nasal tumor or other head and neck cancer have a lower frequency of defective CYP2A6 alleles than a control population. This pilot molecular epidemiological study will test the hypothesis that CYP2A6, a tissue-selective P450 gene known to be expressed in human nasal mucosa and active in the metabolic activation of numerous procarcinogens, plays an important role in the chemical carcinogenesis in the nasal cavity and neighboring organs, including the pharynx, larynx, and the oral cavity, where toxic metabolites formed in the nasal mucosa can be transported. Consequently, individuals with defective CYP2A6 alleles would have a lower risk of developing head and neck cancer. Confirmation of this hypothesis could provide a basis for future chemoprevention efforts using CYP2A6 inhibitors. The outcome of this study will contribute significantly toward a molecular approach to human risk assessment, which is also the goal of the parent grant.